Infection, viral dissemination, and antibody responses of rhesus macaques exposed to the human gammaretrovirus XMRV.

Observed Findings

• XMRV established persistent, disseminated infection with low transient viremia that reactivated at 9 months despite becoming undetectable at ~1 month
• Viral Gag protein was detected throughout multiple tissues, showing wide organ distribution including lymphoid tissue, lung, reproductive tract, and prostate
• XMRV demonstrated organ-specific tropism: CD4+ T cells in lymphoid organs, alveolar macrophages in lung, and epithelial/interstitial cells in other tissues
• Marked lymphocyte activation occurred immediately postinfection, but antigen-specific cellular immune responses were undetectable
• Antibody responses were produced and boosted upon reexposure, but titers declined rapidly, suggesting low ongoing antigen stimulation

Inferred Conclusions

• XMRV can establish a chronic, persistent infection in nonhuman primates with the capacity for viral reactivation after apparent clearance
• The virus disseminates broadly to multiple organ systems with cell-type and tissue-specific targeting patterns
• The immune system mounts detectable antibody responses to XMRV but fails to mount or sustain effective antigen-specific cellular immunity, potentially contributing to chronic infection
• A nonhuman primate model could be useful for studying XMRV pathogenesis, transmission, and potential therapeutic interventions

Remaining Questions